Absorbable polymers are increasingly used in a wide range of biomedical applications including tissue engineering scaffolds, stents, stent coatings, foams, and adhesion prevention barriers. This increased utilization is, in part, a function of the transient nature of these polymers when used as biomedical implants or drug carriers. Medical devices made from bioabsorbable polymers may have the potential to mitigate the inevitable and usually negative physiologic responses (e.g., fibrous encapsulation), which limit long-term device success. Hence, an array of bioabsorbable polymers have been developed and studied in various biomedical applications. While significant research and development activity has been carried out on bioabsorbable polymers, such polymers may suffer from performance deficiencies which are typically not fully recognized until new applications are identified and in-use testing has been carried out. As more uses for these materials are envisioned, an increased demand for bioabsorbable polymers with new and improved properties targeted to address performance deficiencies may be expected to follow.
The majority of bioabsorbable polymers are essentially hard and brittle. Relatively few of these bioabsorbable polymers are elastomeric. As interest in biomedical applications, such as tissue engineering scaffolds, stents, and/or stent coatings, and the like, has increased, bioabsorbable materials exhibiting a wider variety of additional physical properties have been identified to assist the integration of these polymers with the various tissues of the body.
Segmented polyurethane elastomers have enjoyed wide use as biomaterials generally due to their excellent mechanical properties and desirable chemical versatility. However, the vast majority of research devoted to the development of biomedical polyurethanes has focused on long-term applications such as vascular grafts and pacemaker lead insulators. In these types of applications, freedom from significant degradation is necessary to ensure stability of the long-term device. As a consequence, a significant amount of research designed to further inhibit the degradation of polyurethanes has been undertaken. This research indicates that the urethane, urea, and/or ester groups that may be present in a polyurethane or similar polymer have limited susceptibility to chemical and/or enzymatic hydrolysis in biological media. In addition, ether groups often present in the soft segment of a polyurethane or similar polymer may be susceptible to oxidative degradation via phagocyte-derived oxidants. This oxidative degradation is believed to be a key step in the stress cracking phenomenon found in pacemaker lead insulation.
Despite progress in the general development of polyurethanes and similar polymers for use in biomedical applications, relatively little research has been directed to developing bioabsorbable polyurethanes for temporary, rather than longer-term implantation. See Fuller et al., U.S. Pat. No. 4,829,099; Beckmann et al., U.S. Patent Publication Nos. 2005/0013793 A1, 2004/0170597 A1, and 2007/0014755 A1; Bruin et al., PCT Publication No. WO 95/26762; Woodhouse et al., U.S. Pat. No. 6,221,997; Cohn et al., U.S. Pat. No. 4,826,945, which generally discuss recent advances made in the field of bioabsorbable polyurethanes.
Subsequent work by Bruin et al., PCT Publication No. WO 95/26762 discloses the synthesis of crosslinked polyurethane networks incorporating lactide or glycolide and ε-caprolactone joined by a lysine-based diisocyanate. Bruin discloses that these polymers display good elastomeric properties and degrade within about 26 weeks in vitro and about 12 weeks in vivo (subcutaneous implantation in guinea pigs). Despite their disclosed positive flexibility and degradation characteristics, these highly crosslinked polymers are not extensively used in some biomedical applications because they may not be readily processed into surgical articles, for example, using standard techniques such as solution casting or melt processing, as is the case for the more typical linear, segmented polyurethanes.
Cohn et al., EP 295055 discloses a series of elastomeric polyester-polyether-polyurethane block copolymers intended for use as surgical articles. However, these polymers may be relatively stiff and may have low tensile strength, which may preclude their use as elastomeric biomaterials. Beckmann et al., U.S. Patent Publication No. 2005/0013793 A1 describes polyurethane-based biodegradable adhesives from multi-isocyanate functional molecules and multifunctional precursor molecules with terminal groups selected from hydroxyl and amino groups. Woodhouse et al. discloses bioabsorbable polyurethanes derived from amino acids. However, all these bioabsorbable polyurethanes may suffer from one or more of the following drawbacks: (a) the very slow rate of formation of polyurethane that may be attributed to the low reactivity of the polyisocyanates, and (b) the lack of tunable physical and/or mechanical properties and/or controllable hydrolytic degradation profiles for biodegradable polyisocyanates or bioabsorbable polyurethanes derived therefrom.
Fuller et al. (U.S. Pat. No. 4,829,099) disclosed tissue adhesives based on biodegradable polyisocyanates. The synthetic methods used by Fuller et al. to prepare these biodegradable polyisocyanates may be quite cumbersome and/or cost ineffective.
Bezwada (U.S. Patent Application Publication No. 20060188547 A1 and WO 2007030464 A2) disclosed polyurethanes, the corresponding polyisocyanates, and preparations of their manufacture and use wherein the polyurethanes and/or polyisocyanates were reported to be bioabsorbable.
Shaped articles made from polyurethane polymers have been accepted for a variety of applications, including some biomedical applications. Generally speaking, the term “polyurethane” refers to a family of high strength, resilient synthetic polymeric materials containing recurring urethane, urea, and/or ester groups in the polymer backbone. While polyurethane polymers have certain useful properties, shaped articles based on these polymers are not typically bioabsorbable and may therefore be unacceptable in circumstances that require bioabsorption. For example, certain biomedical applications, such as surgical devices including but not limited to monofilament and multifilament sutures, films, sheets, plates, clips, staples, pins, screws, stents, stent coatings, and the like, generally require the use of a material that is bioabsorbable.
In addition, high strength, highly flexible, tough, and durable fibers that possess a prolonged flex fatigue life are needed for use as braided, knitted, woven, or non-woven implants to augment and/or temporarily reinforce autologous tissue grafts or to serve as scaffolds for tissue regeneration.
Other well known uses for bioabsorbable polymers that have not been fully realized or perfected with available polymers of the prior art include scaffolds for tissue engineering, bioabsorbable knitted vascular grafts, drug-releasing devices, growth factor-releasing implants for bone and tissue regeneration, and fiber-reinforced composites for orthopedic applications.
Despite advancements in the art of producing polymeric materials and methods for making polymeric materials suitable for use in stents, stent coatings, scaffolds, films, molded devices, and similar surgical articles, presently available polymers generally lack adequate performance properties desirable in surgical articles, for example, those related to bioabsorption, flex fatigue life, strength in use, flexibility and/or durability. Thus, there continues to be a need for new devices having tunable physical and/or biological properties, so that surgical articles having a variety of end uses can be prepared. The present invention is directed, inter alia, to absorbable stents, stent coatings, scaffolds, and/or flexible films with tunable physical and biological properties and other ends.